Thyroid cancer is one of the most prevalent cancers worldwide, and papillary thyroid cancer (PTC) accounts for >80% of all thyroid cancers. Here we conducted RNA sequencing for 70 PTC and 42 paired-normal tissues in Korean patients, and their transcriptomes were analyzed in various aspects. First, somatic mutations were screened transcriptome-wide throughout samples; BRAF mutation (V600E), which is the most well-established mutation in thyroid cancer, was detected in 47 samples out of 70 (67.14%). HRAS (Q61R, Q61K) and NRAS (Q61R) mutations were shown in two samples, respectively. In gene fusion analysis, we discovered four fusion mutations using our stringent criteria and these include CCDC6-RET and PAX8-PPARG fusions, which have been previously reported for thyroid cancer. Other EZR-ERBB4 and PAX8-GLIS3 fusions are novel fusion mutations found in PTC, and the sample having EZR-ERBB4 mutation was diagnosed as the follicular variant subtype. This is an in-frame mutation and previous reports have shown that ERBB4 is a driver gene for carcinogenesis in multiple types of cancers. In addition, we also found ETV6-NTRK3 fusion in less conservative criteria, which was a well-known fusion in other cancer types. Each fusion mutation above was shown in only one sample, respectively. Through gene expression analysis, we clustered PTC cancer samples into four groups; three of them are shown to be enriched with BRAF V600E mutation, and the other includes samples with NRAS, HRAS mutation. In this study, we thoroughly explored the transcriptome of PTC samples using the next-generation sequencing method and proved well-correlation between mutation and expression profiles. These results not only replicated several findings of previous studies and suggested some novel genes or pathways involved in the PTC development in Koreans.

Citation Format: Seungbok Lee, Hyeon-Gun Jee, Kyu Eun Lee, Jeong-Sun Seo. Transcriptome analysis of papillary thyroid cancer using next-generation sequencing technologies in Korean patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3416. doi:10.1158/1538-7445.AM2014-3416